Cebranopadol
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| Clinical data | |
|---|---|
| ATC code | None |
| Pharmacokinetic data | |
| Biological half-life | ~4.5 hours |
| Identifiers | |
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| CAS Number | 863513-91-1 |
| PubChem (CID) | 11848225 |
| ChemSpider | 29398942 |
| Chemical and physical data | |
| Formula | C24H27FN2O |
| Molar mass | 378.482 g/mol |
| 3D model (Jmol) | Interactive image |
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Cebranopadol (GRT-6005) is a novel opioid analgesic of the benzenoid class which is currently under development internationally by Grünenthal, a German pharmaceutical company, and its partner Depomed, a pharmaceutical company in the United States, for the treatment of a variety of different acute and chronic pain states.[1][2][3] As of November 2014, it is in phase III clinical trials. Cebranopadol is unique in its mechanism of action as an opioid, binding to and activating all four of the opioid receptors; it acts as a full agonist of the nociceptin receptor (Ki = 0.9 nM; EC50 = 13.0; IA = 89%), μ-opioid receptor (Ki = 0.7 nM; EC50 = 1.2; IA = 104%), and δ-opioid receptor (Ki = 18 nM; EC50 = 110; IA = 105%), and as a partial agonist of the κ-opioid receptor (Ki = 2.6 nM; EC50 = 17; IA = 67%).[1] The ED50 values of 0.5-5.6 µg/kg when introduced IV & 25.1 µg/kg after oral administration.[4]
Cebranopadol shows highly potent and effective antinociceptive and antihypertensive effects in a variety of different animal models of pain.[1] Notably, it has also been found to be more potent in models of chronic neuropathic pain than acute nociceptive pain compared to selective μ-opioid receptor agonists.[1] Relative to morphine, tolerance to the analgesic effects of cebranopadol has been found to be delayed (26 days versus 11 days for complete tolerance).[1] In addition, unlike morphine, cebranopadol has not been found to affect motor coordination or reduce respiration in animals at doses in or over the dosage range for analgesia.[1] As such, it may have improved and prolonged efficaciousness and greater tolerability in comparison to currently available opioid analgesics.[1]
As an agonist of the κ-opioid receptor, cebranopadol may have the capacity to produce psychotomimetic effects and other adverse reactions at sufficiently high doses, a property which could potentially limit its practical clinical dosage range.[5]
See also
References
- 1 2 3 4 5 6 7 Linz K, Christoph T, Tzschentke TM, et al. (June 2014). "Cebranopadol: a novel potent analgesic nociceptin/orphanin FQ peptide and opioid receptor agonist". J. Pharmacol. Exp. Ther. 349 (3): 535–48. doi:10.1124/jpet.114.213694. PMID 24713140.
- ↑ Schunk S, Linz K, Hinze C, et al. (August 2014). "Discovery of a Potent Analgesic NOP and Opioid Receptor Agonist: Cebranopadol". ACS Med Chem Lett. 5 (8): 857–62. doi:10.1021/ml500117c. PMID 25147603.
- ↑ Lambert DG, Bird MF, Rowbotham DJ (September 2014). "Cebranopadol: a first in-class example of a nociceptin/orphanin FQ receptor and opioid receptor agonist". Br J Anaesth. 114: 364–6. doi:10.1093/bja/aeu332. PMID 25248647.
- ↑ Cebranopadol: a novel potent analgesic nociceptin/orphanin FQ peptide and opioid receptor agonist. Journal of Pharmacol Exp Ther. 2014 Jun;349(3):535-48. doi: 10.1124/jpet.114.213694
- ↑ Pfeiffer A, Brantl V, Herz A, Emrich HM (August 1986). "Psychotomimesis mediated by kappa opiate receptors". Science. 233 (4765): 774–6. doi:10.1126/science.3016896. PMID 3016896.